Impact of acute kidney injury exposure period among liver transplantation patients

Background: Acute kidney injury is a common complication of liver transplantation. in this single-centre retrospective observational study, we investigated the impact of acute kidney disease on liver recipient survival.Methods: the study population consisted of patients who underwent a liver engraftment between January 2002 and November 2006, at a single transplantation centre in São Paulo, Brazil. Acute kidney injury diagnosis and staging were according to the recommendations of the Acute Kidney Injury Network and consisted of scanning the daily serum creatinine levels throughout the hospital stay. Patients requiring renal replacement therapy prior to transplantation, those who developed acute kidney injury before the procedure or those receiving their second liver graft were excluded from the study.Results: A total of 444 liver transplantations were performed during the study period, and 129 procedures (29%) were excluded. the remaining 315 patients constituted the study population. in 207 procedures, the recipient was male (65%). the mean age of the population was 51 years. Cumulative incidence of acute kidney injury within 48 h, during the first week after transplantation, and throughout the hospital stay was 32, 81 and 93%, respectively. Renal replacement therapy was required within a week after the transplantation in 31 procedures (10%), and another 17 (5%) required replacement therapy after that period. Mean follow-up period was 2.3 years. Time in days from acute kidney injury diagnosis to initiation of replacement therapy or reaching serum creatinine peak was associated with lower overall survival even when adjusted for significant potential confounders (HR 1.03; 95% CI 1.01, 1.05; p=0.002). Overall, patients experiencing acute kidney injury lasting for a week or more before initiation of replacement therapy experienced a threefold increase in risk of death (HR 3.02; 95% CI 2.04, 4.46; p<0.001).Conclusions: Acute kidney injury after liver transplantation is remarkably frequent and has a substantial impact on patient survival. Delaying the initiation of renal replacement therapy in such population may increase mortality by more than 20% per day.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilHosp Transplantes Euryclides de Jesus Zerbini, Liver Unit, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilTufts Univ, New England Med Ctr, Div Nephrol, Medford, MA 02155 USAUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

Effects of simvastatin on cytokines secretion from mononuclear cells from critically ill patients with acute kidney injury

Purpose: To assess the in vitro effects of simvastatin on IL-10 and TNF-alpha secretion from peripheral blood mononuclear cells (PBMC) of critically ill patients with and without acute kidney injury (AKI).Methods: PBMC were collected from 63 patients admitted to the intensive care unit (ICU) and from 20 healthy controls. Patients were divided in 3 subgroups: with AKI, with sepsis and without AKI and with AKI and sepsis. After isolation by ficoll-gradient centrifugation cells were incubated in vitro with LPS 1 ng/mL, simvastatin (10(-8)M) and with LPS plus simvastatin for 24 h. TNF-alpha and IL-10 concentrations on cells surnatant were determined by ELISA.Results: Cells isolated from critically ill patients showed a decreased spontaneous production of TNF-alpha and IL-10 compared to healthy controls (6.7(0.2-12) vs 103(64-257) pg/mL and (20 (13-58) vs 315(105-510) pg/mL, respectively, p < 0.05). Under LPS-stimulus, IL-10 production remains lower in patients compared to healthy control (451 (176-850) vs 1150(874-1521) pg/mL,p < 0.05) but TNF-alpha production was higher (641 (609-841) vs 406 (201-841) pg/mL, p < 0.05). the simultaneous incubation with LPS and simvastatin caused decreased IL-10 production in cells from patients compared to control (337 (135-626) vs 540 (345-871) pg/mL, p < 0.05) and increased TNF-alpha release (711 (619-832) vs 324 (155-355) pg/mL, p < 0.05). Comparison between subgroups showed that the results observed in TNF-alpha and IL-10 production by PBMC from critically ill patients was independent of AKI occurrence.Conclusions: the PBMC treatment with simvastatin resulted in attenuation on pro-inflammatory cytokine spontaneous production that was no longer observed when these cells were submitted to a second inflammatory stimulus. Our study shows an imbalance between pro and anti-inflammatory cytokine production in PBMC from critically ill patients regardless the presence of AKI. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto de Ensino e Pesquisa do Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilIAEH IEP Hosp Israelita Albert Einstein Inst Ensi, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilWeb of Scienc

Serum soluble-Fas is a predictor of red blood cell transfusion in critically ill patients

OBJECTIVE: To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury. METHODS: We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated. RESULTS: Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01). CONCLUSIONS: Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.OBJETIVO: Investigar a relação entre a transfusão de hemácias e os níveis séricos de Fas solúvel, eritropoietina e citocinas inflamatórias em pacientes gravemente enfermos, com e sem insuficiência renal aguda. MÉTODOS: Os seguintes grupos foram estudados: pacientes gravemente enfermos com insuficiência renal aguda (n=30) e sem insuficiência renal aguda (n=13), pacientes portadores de doença renal crônica terminal em hemodiálise (n=25) e indivíduos saudáveis (n=21). Os níveis séricos de Fas solúvel, eritropoietina, interleucina 6, interleucina 10 e ferro, além da concentração de hemoglobina e de hematócrito, foram analisados em todos os grupos. A associação entre tais variáveis foram estudadas nos pacientes gravemente enfermos. RESULTADOS: Os níveis séricos de eritropoietina mostraram-se mais elevados nos pacientes gravemente enfermos do que nos dos demais grupos. Concentrações mais baixas de hemoglobina foram documentadas nos pacientes com insuficiência renal aguda em relação aos demais. Níveis séricos mais elevados de Fas solúvel foram observados nos pacientes com insuficiência renal aguda e doença renal crônica terminal. Pacientes gravemente enfermos transfundidos apresentaram níveis séricos mais elevados de Fas solúvel (5.906±2.047 e 1.920±1.060; p<0,001), interleucina 6 (518±537 e 255±502; p=0,02), interleucina 10 (35,8±30,7 e 18,5±10,9; p=0,02) e ferro, além de maior mortalidade em 28 dias. Os níveis séricos de Fas solúvel mostraram-se independentemente associados ao número de transfusões (p=0,02). O nível sérico de Fas solúvel foi um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos (p=0,01). CONCLUSÃO: O nível sérico de Fas solúvel é um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos, com ou sem insuficiência renal aguda. Mais estudos clínicos e laboratoriais são necessários para confirmar tal resultado.Universidade Federal de São Paulo (UNIFESP)Hospital Israelita Albert EinsteinUNIFESPSciEL

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity

Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univiversidade Federal de Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Rua Pedro de Toledo,740,2 Andar, Sao Paulo, Brazil.FAPESP: 08/09773-4Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES).Web of Scienc

Expression of adenosine triphosphate-sensitive potassium channels in rats with cirrhosis: correlationship with sympathetic activity and renal function

Objective: The aim of this study was to perform a direct analysis ofKATP mRNA expression by RT-PCR in kidney and isolated aorta fromrats with cirrhosis (induced by carbon tetrachloride) and controls.The present study also analyses the relation between induced cirrhosisand urinary excretion of sodium and sympathetic activity in cirrhoticrats. Methods: Rats were placed in metabolic cages and allowedfree access to food and water. Cirrhosis was induced by repeateddoses of carbon tetrachloride by gastric gavage. After some weeks,the kidney and aorta were dissected and utilized for RNA extraction.Blood and urine were analyzed for electrolytes. Renal function wasestimated by creatinine clearance and sodium urinary excretion.Serum catecholamines were measured by HPLC analysis. Results:First, RT-PCR analysis showed that KATP mRNA is expressed in liverwith cirrhosis and intense fibrosis, but not with moderate fibrosis.Second, RT-PCR analysis revealed that KATP mRNA was detectedonly in aorta dissected from rats with cirrhosis. Finally, an enhancedreabsorption of sodium without renal failure suggests a potentialmediator would increase the activity of the sympathetic system.Conclusion: These results suggest that KATP mRNA is expressed incirrhotic rats with sympathetic activation and renal dysfunction. Thischannel might be involved in another route where the vascular tonecan be modulated in cirrhosis

The impact of continuous renal replacement therapy on renal outcomes in dialysis-requiring acute kidney injury may be related to the baseline kidney function

Abstract Background Many controversies exist regarding the management of dialysis-requiring acute kidney injury (D-AKI). No clear evidence has shown that the choice of dialysis modality can change the survival rate or kidney function recovery of critically ill patients with D-AKI. Methods We conducted a retrospective study investigating patients (≥16 years old) admitted to an intensive care unit with D-AKI from 1999 to 2012. We analyzed D-AKI incidence, and outcomes, as well as the most commonly used dialysis modality over time. Outcomes were based on hospital mortality, renal function recovery (estimated glomerular filtration rate-eGFR), and the need for dialysis treatment at hospital discharge. Results In 1,493 patients with D-AKI, sepsis was the main cause of kidney injury (56.2%). The comparison between the three study periods, (1999–2003, 2004–2008, and 2009–2012) showed an increased in incidence of D-AKI (from 2.56 to 5.17%; p = 0.001), in the APACHE II score (from 20 to 26; p < 0.001), and in the use of continuous renal replacement therapy (CRRT) as initial dialysis modality choice (from 64.2 to 72.2%; p < 0.001). The mortality rate (53.9%) and dialysis dependence at hospital discharge (12.3%) remained unchanged over time. Individuals who recovered renal function (33.8%) showed that those who had initially undergone CRRT had a higher eGFR than those in the intermittent hemodialysis group (54.0 × 46.0 ml/min/1.73 m2, respectively; p = 0.014). In multivariate analysis, type of patient, sepsis-associated AKI and APACHE II score were associated to death. For each additional unit of the APACHE II score, the odds of death increased by 52%. The odds ratio of death for medical patients with sepsis-associated AKI was estimated to be 2.93 (1.81–4.75; p < 0.001). Conclusion Our study showed that the incidence of D-AKI increased with illness severity, and the use of CRRT also increased over time. The improvement in renal outcomes observed in the CRRT group may be related to the better baseline kidney function, especially in the dialysis dependence patients at hospital discharge